Study to assess the efficacy and safety of Adjuvant Osimertinib in NSCLC with Uncommon EGFRm

Exclusion Criteria

• 1. Previous enrollment and treatment in the present study.
• 2. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 8 weeks prior to enrollment, or concurrent enrollment and exposure in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• 3. Treatment with any of the following:
• - Pre-operative or post-operative or planned radiation therapy for the current lung cancer.
• - Pre-operative (neo-adjuvant) platinum based or other chemotherapy.
• - Any prior anticancer therapy, including investigational therapy, for treatment of NSCLC other than standard platinum based doublet post-operative adjuvant chemotherapy.
• - Prior treatment with neoadjuvant or adjuvant EGFR-TKI.
• - Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks of the first dose of study drug.
• - Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior) (Appendix F). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
• - Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
• 4. Patients who have had only segmentectomies or wedge resections.
• 5. History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
• 6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
• • Screening for chronic conditions is not required.
• • Active infection will include any patients receiving treatment for infection.
• • Subjects with a resolved or chronic infection HBV are eligible if they are:
• a) Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc IgG] or
• b) Positive for HBsAg, negative for HBeAg but for > 6 months have had transaminases levels below ULN and HBV DNA levels ≤ 100 IU/mL (i.e., are in an inactive carrier state). Refer to Restrictions, Section 5.3.
• 7. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib.
• 8. Any of the following cardiac criteria:
• - Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.
• - Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, third-degree heart block, second-degree heart block.
• - Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities* including:
• - Serum/plasma potassium < LLN
• - Serum/plasma magnesium < LLN
• - Serum/plasma calcium < LLN
• heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes (TdP) .
• *Note: Correction of electrolyte abnormalities to within normal ranges can be performed during the screening period.
• 9. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• 10. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• - Absolute neutrophil count <1.5 × 109/L.
• - Platelet count <100 × 109/L.
• - Haemoglobin <90 g/L.
• - Alanine aminotransferase (ALT) >2.5× the upper limit of normal (ULN).
• - Aspartate aminotransferase (AST) >2.5 × ULN.
• - Total bilirubin >1.5 × ULN or >3 × ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia).
• - Creatinine >1.5 × ULN concurrent with creatinine clearance <50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN.
• 11. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
• 12. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
• 13. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca representative and/or staff at the study site).
• 14. Currently pregnant (confirmed with positive pregnancy test) or breast feeding.
• In addition, the following are considered criteria for exclusion from the exploratory molecular research only:
• 1. Prior allogeneic bone marrow transplant.
• 2. Non-leukocyte depleted whole blood transfusion within 120 days of sample collection.